1. Field of the Invention
This invention relates to 12 substituted prostaglandins that possess utility as luteolytic agents and for other pharmaceutical purposes.
2. Description of the Prior Art
Prostaglandins are natural hormones found in the human body. Various types of prostaglandins have been synthesized previously. Among the known properties of certain forms of prostaglandins are their capability to induce abortion in humans, their ability to function as regulators of muscle activity, lipid metabolism and certain other aspects of the reproductive process. It is also believed that they effect dilation of blood vessels, thereby reducing blood pressure. They are also believed to effect bronchial dilation. One of the problems with the natural substances has been the difficulty in separating the various biological activities in order to measure the effectiveness in respect of each independent property.
Fluorine has previously been substituted in the prostaglandin molecules. U.S. Pat. No. 3,833,640 discloses fluorine substitution near the end of the alkyl chain. See also U.S. Pat. Nos. 3,879,439; 3,969,378; 3,954,851 and 3,944,595. U.S. Pat. No. 3,935,241 discloses substitution of "CH.sub.2 X" at the 11 position, wherein X may be fluoro, chloro, bromo or others.
Methyl substitution in the nucleus of prostaglandins have been known. See U.S. Pat. Nos. 3,514,383; 3,935,241; 3,953,499 and 3,505,387. See also the article entitled "A Synthesis of 12-Substituted Prostaglandins" by Norio Nakamura and Kiyoshi Saki as published in the United Kingdom by Pergamon Press in Tetrahedron Letters No. 24, Pages 2049-2052 (1976), which reports the synthesis of 11-deoxy-12.alpha.-methyl prostaglandin E.sub.2 and 11-deoxy-12.alpha.-hydroxymethyl prostaglandin E.sub.2.
Non-nuclear methyl substitution has been disclosed in U.S. Pat. Nos. 3,728,382; 3,813,433 and 3,888,919.
Bromine substitution has been disclosed in U.S. Pat. Nos. 3,755,426; 3,912,725; 3,833,640; 3,935,241 and 3,944,595.
There has, therefore, been lacking a disclosure of any fluorine substituted in prostaglandins in the five-member ring nucleus. More specifically, there has been lacking a 12 substituted fluoro-prostaglandin, the method of making the same and the unique antifertility properties of the same.